Background: Federally sponsored cancer clinical trials (FS-CCTs) address a broad set of clinical cancer research questions that are avoided by industry sponsors, including combining treatment modalities, examining whether approved drugs may work in other cancers, or examining de-escalation therapy. FS-CCTs routinely extend the lives of patients with cancer and inform treatment guidelines. However, FS-CCTs must often be conducted in partnership with industry sponsors since the cost of drugs is high and cannot be paid for by the government. This limits the independence of FS-CCTs. We aimed to examine the drug costs for trials with federal sponsorship. Methods: We included all US-based cancer treatment trials registered in ClinicalTrials.gov that examined pharmaceuticals and/or biological products and started from 2018-2022. Trials with any NIH or other federal sponsorship (as the sole, lead, or other sponsor) were included. Drug names and number of enrollments per arm and drug were extracted from ClinicalTrials.gov and study protocols. The Wholesale Acquisition Cost (WAC) was obtained from IBM Micromedex RED BOOK (2023) by matching the product name, dose strength and administration route. The product acquisition cost (“cost”) per trial was computed by summing the WAC for each drug and multiplying by the number of enrollments. Results: Overall, N=1020 trials were examined (phase I = 343, phase II = 611, phase III = 66). The mean (median) drug costs were $53.9 million (m) ($7.4m) overall, including $73.8m ($19.8m), $47.2m ($8.7m), and $44.7m ($5.8m) for trials solely sponsored, led by, or with secondary/tertiary participation by federal sponsors, respectively. Trial-level drug costs were $19.2m ($3.6m), $51.9m ($9.4m), and $244.9m ($38.8m) for phase I, II, and III trials, respectively. Drug costs were much greater for trials involving immune and/or targeted therapies ($60.1m [$11.4m]) than those with conventional chemotherapies ($30.8m [$1.5m]). In the subset of n=128 phase 2 or 3 comparative trials, drug costs were $97.7m ($21.8m) for experimental arms and $24.1m ($1.4m) for control arms. Conclusions: The costs for drugs in FS-CCTs were very high, especially for the experimental arms, highlighting the necessity for federally sponsored researchers to collaborate with industry partners to conduct trials. Drug costs for immune and/or targeted therapies were higher yet, suggesting that the cost burden to conduct trials for federal sponsors may continue to increase. These findings also suggest that systemwide costs for cancer drugs in clinical practice will continue to increase substantially. These results have implications for how FS-CCTs are designed and conducted, since the necessity of collaboration between federal and industry sponsors likely limits the independence of federal research. Future public policy efforts should focus on mechanisms for independent investigation of new pharmacologic agents.